tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of the Anti–PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study
Authors: Jusheng An, Jie Tang, Benjamin X. Li, Huihua Xiong, Hui Qiu, Lin Luo, Li Wang, Danbo Wang, Qi Zhou, Qin Xu, Honglin Song, Yunyan Zhang, Hongping Zhang, Yujie Li, Xiaohui Yu, Jing Zhang, Rachel Ng, Wayne Zhao, Michael Wong, Xiangrong Dai, Guiling Li, Lingying Wu
Journal: Clinical Cancer Research (2022)

Abstract Purpose: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti–programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer. Patients and Methods: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1–positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%–24.5%]. Median PFS was 4.44 months (95% CI, 2.37–5.75 months), and the median OS was 14.72 months (95% CI, 9.59–NE months). ORR of PD-L1–positive patients was 16.7%, and the ORR of PD-L1–negative patients was 17.9%. No treatment-related deaths occurred. Conclusions: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti–PD-1/PD-L1 mAbs.
Effect of prone positioning without mechanical ventilation in COVID-19 patients with acute respiratory failure
Authors: Yanfei Shen, Shangzhong Chen, Caibao Hu
Journal: European Respiratory Journal (2022)

<b>The mechanism of prone positioning in COVID-19 is quite different from that in ARDS and the severity of respiratory failure plays a key role in the efficacy of prone positioning in COVID-19</b>https://bit.ly/3Qf9Prw
Preclinical and Clinical Trial Results Using Talazoparib and Low-Dose Chemotherapy
Authors: Zev A. Wainberg, Arun S. Singh, Gottfried E. Konecny, Kelly E. McCann, J. Randolph Hecht, Jonathan Goldman, Bartosz Chmielowski, Richard S. Finn, Neil O'Brien, Erika Von Euw, Megan M. Price, Diego Martinez, Lisa Yonemoto, Meghan Brennan, John A. Glaspy, Dennis J. Slamon
Journal: Clinical Cancer Research (2022)

Abstract Purpose: On the basis of preclinical data, we hypothesized that low doses of chemotherapy (10% of therapeutic doses) with full dose of a PARP inhibitor could have improved efficacy and tolerability. Patients and Methods: In this phase I dose-escalation study, patients with BRCA-normal advanced malignancies were assigned to either talazoparib/temozolomide or talazoparib/irinotecan. Talazoparib was dose-escalated from 500 mcg to 1 mg daily before dose escalation of temozolomide/irinotecan. The starting dose of temozolomide was 25 mg/m2/day orally on days 1 to 5 and irinotecan was 25 mg/m2/day intravenously on days 1 and 15. The primary objectives of this trial were safety and tolerability, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD). Results: Of 40 patients enrolled, 18 (mean: 7 prior therapies) were enrolled in talazoparib + temozolomide and 22 in talazoparib + irinotecan. DLTs were hematologic in both arms, but all hematologic adverse events resolved with either treatment interruption and/or dose reductions of talazoparib. The MTDs were talazoparib 1 mg + temozolomide 37.5 mg/m2 and talazoparib 1 mg + irinotecan 37.5 mg/m2. There were four partial responses in the talazoparib + temozolomide arm and five in the talazoparib + irinotecan arm for a response rate of 23% (9/40). The pharmacokinetic profiles of talazoparib + temozolomide/irinotecan were similar to that of talazoparib monotherapy. Responses were seen independent of homologous recombination (HR) status and HR deficiency score. Conclusions: These results show that talazoparib with low-dose temozolomide or irinotecan is reasonably well tolerated and demonstrates clinical activity in a wide range of cancers. Randomized trials of talazoparib with or without low-dose chemotherapy are ongoing in small cell lung cancer and ovarian cancer.
Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
Authors: Kiho Son, Rameen Jamil, Abhiroop Chowdhury, Manan Mukherjee, Carmen Venegas, Kate Miyasaki, Kayla Zhang, Zil Patel, Brittany Salter, Agnes Che Yan Yuen, Kevin Soon-Keen Lau, Braeden Cowbrough, Katherine Radford, Chynna Huang, Melanie Kjarsgaard, Anna Dvorkin-Gheva, James Smith, Quan-Zhen Li, Susan Waserman, Christopher J Ryerson, Parameswaran Nair, Terence Ho, Narayanaswamy Balakrishnan, Ishac Nazy, Dawn ME Bowdish, Sarah Svenningsen, Chris Carlsten, Manali Mukherjee
Journal: European Respiratory Journal (2022)

Background Autoimmunity has been reported in patients with severe COVID-19. We investigated whether antinuclear/extractable-nuclear antibodies (ANAs) were present up to a year after infection, and if they were associated with the development of clinically relevant Post-Acute Sequalae of COVID-19 (PASC) symptoms. Methods A rapid assessment line immunoassay was used to measure circulating levels of ANA/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6, and 12 months post-recovery. Patient-reported fatigue, cough, and dyspnea were recorded at each timepoint. Multivariable logistic regression model and receiver-operating curves (ROC) were used to test the association of autoantibodies with patient-reported outcomes and pro-inflammatory cytokines. Results Compared to age- and sex-matched healthy controls (n=22) and those who had other respiratory infections (n=34), patients with COVID-19 had higher detectable ANAs at 3 months post-recovery (p&lt;0.001). The mean number of ANA autoreactivities per individual decreased from 3 to 12 months (3.99 to 1.55) with persistent positive titers associated with fatigue, dyspnea, and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p&lt;0.028, AUC=0.86) and dyspnea (p&lt;0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNFα) and C-reactive protein predicted the elevated ANAs at 12 months. TNFα, D-dimer, and IL-1β had the strongest association with symptoms at 12 months. Regression analysis showed TNFα predicted fatigue (β=4.65, p=0.004) and general symptomaticity (β=2.40, p=0.03) at 12 months. Interpretation Persistently positive ANAs at 12 months post-COVID are associated with persisting symptoms and inflammation (TNFα) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.
Reply to: Nebulised liposomal amphotericin-B: a promising strategy for preventing ABPA relapse
Authors: Cendrine Godet, Jacques Cadranel, Jean-Pierre Frat, Stéphanie Ragot, Francis Couturaud
Journal: European Respiratory Journal (2022)

Regarding their first comment on the study population, we acknowledge that a maintenance treatment might be more warranted and even more effective in patients with previous recurrent exacerbations than in patients without previous exacerbation. In our study, this hypothesis was supported by our analysis, which was restricted to patients with previous exacerbations ( i.e. in the past years). During the 24-month follow-up period, we found that in patients with at least one previous severe exacerbation before inclusion, the proportion with at least two or more severe exacerbations was 27% in the active treatment group as compared to 53% in the placebo group (p=0.03) [1]. However, in the setting of our randomised trial, we decided to include a well-defined population and to explore without "a priori" the impact of a maintenance treatment following a homogeneous attack treatment. In fact, the presence or absence of previous exacerbations might not be the only factor influencing the effect of maintenance therapy. For example, according to the computed tomography (CT) scan phenotype at inclusion [2], it could be interesting to evaluate the benefit of a maintenance strategy and its influence on future relapse or complete remission. Another interesting issue could be the impact of predictive factors, such as high-attenuation mucus impactions, on future relapses or complete remission. Is nebulised liposomal amphotericin-B a promising strategy for preventing allergic bronchopulmonary aspergillosis relapse? <https://bit.ly/3qTDMCA>
Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery
Authors: Piotr Harbut, G. Kim Prisk, Robert Lindwall, Sarah Hamzei, Jenny Palmgren, Catherine E. Farrow, Goran Hedenstierna, Terence C. Amis, Atul Malhotra, Peter D. Wagner, Kristina Kairaitis
Journal: European Respiratory Journal (2022)

Background Pathological evidence suggests that coronavirus disease 2019 (COVID-19) pulmonary infection involves both alveolar damage (causing shunt) and diffuse microvascular thrombus formation (causing alveolar dead space). We propose that measuring respiratory gas exchange enables detection and quantification of these abnormalities. We aimed to measure shunt and alveolar dead space in moderate COVID-19 during acute illness and recovery. Methods We studied 30 patients (22 males; mean± sd age 49.9±13.5 years) 3–15 days from symptom onset and again during recovery, 55±10 days later (n=17). Arterial blood (breathing ambient air) was collected while exhaled oxygen and carbon dioxide concentrations were measured, yielding alveolar–arterial differences for each gas ( P A−aO 2 and P a−ACO 2 , respectively) from which shunt and alveolar dead space were computed. Results For acute COVID-19 patients, group mean (range) for P A−aO 2 was 41.4 (−3.5–69.3) mmHg and for P a−ACO 2 was 6.0 (−2.3–13.4) mmHg. Both shunt (% cardiac output) at 10.4% (0–22.0%) and alveolar dead space (% tidal volume) at 14.9% (0–32.3%) were elevated (normal: &lt;5% and &lt;10%, respectively), but not correlated (p=0.27). At recovery, shunt was 2.4% (0–6.1%) and alveolar dead space was 8.5% (0–22.4%) (both p&lt;0.05 versus acute). Shunt was marginally elevated for two patients; however, five patients (30%) had elevated alveolar dead space. Conclusions We speculate impaired pulmonary gas exchange in early COVID-19 pneumonitis arises from two concurrent, independent and variable processes (alveolar filling and pulmonary vascular obstruction). For most patients these resolve within weeks; however, high alveolar dead space in ∼30% of recovered patients suggests persistent pulmonary vascular pathology.
Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis
Authors: Mingjin Yang, Yishi Li, Youfan Jiang, Shuliang Guo, Jian-Qing He, Don D. Sin
Journal: European Respiratory Journal (2022)

Introduction Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting β2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD. Methods Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke. Results A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% versus 1.3%; relative risk 1.42, 95% CI 1.11–1.81) and triple therapy (1.6% versus 1.4%; relative risk 1.29, 95% CI 1.03–1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was &gt;1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power. Conclusion Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of &gt;1% per year.
The Unwritten Code
Authors: Anna W. LaVigne
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Etirinotecan Pegol Treatment for Patients With Metastatic Breast Cancer and Brain Metastases
Authors: Bin Zhang, Shuixing Zhang
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Short- and long-term noninvasive cardiopulmonary exercise assessment in previously hospitalised COVID-19 patients
Authors: Inderjit Singh, Phillip Joseph
Journal: European Respiratory Journal (2022)

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has had a staggering impact on the global healthcare system [1]. It was estimated that by November 2021, over 3 billion individuals or 44% of the world's population had been infected with SARS-CoV-2 at least once [2]. A substantial number of survivors of COVID-19 exhibit chronic signs and symptoms of multisystemic illness [3, 4]. This so-called Post-Acute Sequelae of SARS-CoV-2 infection (or PASC) syndrome describes a phenomenon that ranges from persistent neurocognitive deficits to cardiorespiratory symptoms beyond 4 weeks from acute disease onset [1].
Subacute Abdominal Pain in a Patient With Chronic Liver Disease and Hepatocellular Carcinoma
Authors: Binbin Zheng-Lin, David M. Faleck, James J. Harding
Journal: JAMA Oncology (2022)

A 66-year-old woman with chronic hepatitis B infection and hepatocellular carcinoma presented with moderate radiating epigastric pain with nausea, anorexia, and water brash without emesis. What is your diagnosis?
Etirinotecan Pegol Treatment for Patients With Metastatic Breast Cancer and Brain Metastases—Reply
Authors: Debu Tripathy, Sara M. Tolaney, Mary Tagliaferri
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
High antigen density of BCMA: friend or foe to CAR T cells?
Authors: Mahmoud R Gaballa, Marcela V Maus
Journal: Journal for ImmunoTherapy of Cancer (2022)

The therapeutic landscape of multiple myeloma (MM) has been rapidly evolving with the development of newer modalities such as chimeric antigen receptor T-cell (CAR-T) therapies. Currently, there are two CAR-T cell products approved by the U.S. Food and Drug Administration for MM, idecabtagene
Feasibility of unsedated lung MRI in young children with cystic fibrosis
Authors: C. Corin Willers, Bettina S. Frauchiger, Enno Stranzinger, Grzegorz Bauman, Alexander Moeller, Andreas Jung, Andreas Hector, Nicolas Regamey, Maura Zanolari, Dominik Mueller-Suter, Alena Lioba Kuhn, Sylvain Blanchon, Isabelle Rochat, Philipp Latzin, Kathryn A. Ramsey
Journal: European Respiratory Journal (2022)

<b>Lung MRI could serve as a sensitive surveillance method in young childhood. We found that unsedated lung MRI is feasible in young children with cystic fibrosis. Feasibility increases with age and was comparable with lung function tests.</b>https://bit.ly/3LbCGvt
Nebulised liposomal amphotericin-B: a promising strategy for preventing ABPA relapse
Authors: Yang Liu, Hai-Wen Lu, Jin-Fu Xu
Journal: European Respiratory Journal (2022)

<b>Nebulised liposomal amphotericin-B may play an important role in the treatment of ABPA. Studies aimed at evaluating the efficacy of nebulised liposomal amphotericin-B on ABPA relapse are urgently needed in the near future.</b> https://bit.ly/3RpV7yK
Air pollutants, genetic susceptibility and risk of incident idiopathic pulmonary fibrosis
Authors: Feipeng Cui, Yu Sun, Junqing Xie, Dankang Li, Mingyang Wu, Lulu Song, Yonghua Hu, Yaohua Tian
Journal: European Respiratory Journal (2022)

Air pollutants are considered as non-negligible risk factors of idiopathic pulmonary fibrosis (IPF). However, the relationship between long-term air pollution and the incidence of IPF is unknown. Our objective was to explore the associations of air pollutants with IPF risk and further assess the modification effect of genetic susceptibility.We used land-use regression model estimated concentrations of nitrogen dioxide (NO2), nitrogen oxides (NO x ) and particulate matter (fine particulate matter with diameter <2.5 μm (PM2.5) and particulate matter with diameter <10 μm (PM10)). The polygenic risk score (PRS) was constructed using 13 independent single nucleotide polymorphisms. Cox proportional hazard models were used to evaluate the associations of air pollutants with IPF risk and further investigate the modification effect of genetic susceptibility. Additionally, absolute risk was calculated.Among 433 738 participants from the UK Biobank, the incidence of IPF was 27.45 per 100 000 person-years during a median follow-up of 11.78 years. The adjusted hazard ratios of IPF for each interquartile range increase in NO2, NO x and PM2.5 were 1.11 (95% CI 1.03-1.19), 1.07 (95% CI 1.01-1.13) and 1.09 (95% CI 1.02-1.17), respectively. PM2.5 had the highest population attribution risk, followed by NO x and NO2. There were additive interactions between NO2, NO x and PM2.5 and genetic susceptibility. Participants with a high PRS and high air pollution had the highest risk of incident IPF compared with those with a low PRS and low air pollution (adjusted hazard ratio: NO2 3.94 (95% CI 2.77-5.60), NO x 3.08 (95% CI 2.21-4.27), PM2.5 3.65 (95% CI 2.60-5.13) and PM10 3.23 (95% CI 2.32-4.50)).Long-term exposures to air pollutants may elevate the risk of incident IPF. There are additive effects of air pollutants and genetic susceptibility on IPF risk.
Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome
Authors: Rebecca C. Simpson, Erin R. Shanahan, Marcel Batten, Irene L. M. Reijers, Mark Read, Ines P. Silva, Judith M. Versluis, Rosilene Ribeiro, Alexandra S. Angelatos, Jian Tan, Chandra Adhikari, Alexander M. Menzies, Robyn P. M. Saw, Maria Gonzalez, Kerwin F. Shannon, Andrew J. Spillane, Rebecca Velickovic, Alexander J. Lazar, Ashish V. Damania, Aditya K. Mishra, Manoj Chelvanambi, Anik Banerjee, Nadim J. Ajami, Jennifer A. Wargo, Laurence Macia, Andrew J. Holmes, James S. Wilmott, Christian U. Blank, Richard A. Scolyer, Georgina V. Long
Journal: Nature Medicine (2022)
Inhibition of SARS-CoV-2 Omicron BA.1 and BA.4 Variants After Fourth Vaccination or Tixagevimab and Cilgavimab Administration in Patients With Cancer
Authors: Maximilian J. Mair, Manfred Mitterer, Pia Gattinger, Julia M. Berger, Rudolf Valenta, Dominic Fong, Matthias Preusser
Journal: JAMA Oncology (2022)

This cohort study assesses the capacity of passive immunization and tixagevimab and cilgavimab to inhibit interaction between receptor-binding domains and angiotensin-converting enzyme 2 in patients with hemato-oncologic diseases.